Preparation of aromatic mercury halides



Patented Apr. 15, 1952 UNITED STATES PATENT OFFICE PREPARATIONOFAROMATIC. MERCUR HALIDES Otto Dank and Jaroslav Nosek, Pardubice-Rybitvi, Czechoslovakia, assignors to Vychodoceske Chemicke Zavody,narodni podnik, Pardubice, Czechoslovakia No Drawing. Application March9, 1951, Serial No. 214,852. In Czechoslovakia February 19,

16 Claims. (01. 260-433) "The present invention relates to themanufaction of benzene diazonium chloride (diazotized aniline) isintroduced with a solutionof mercury chloride into dilute hydrochloricacid whereby a double salt is formed which is filtered with suction.This double salt is then introduced into acetone and decomposed by meansof two equivalents of powdered copper (two gram-atoms copper to 1gram-molecule of double compound), and the phenyl mercury chlorideformed is extracted with acetone to separate it from the insolublecuprous chloride also formed during the reaction; The yield obtained'byNesmajanovs process is 51% of the theoretical yield. Thereactionproceeds in accordance with the following equations wherein R.represents an aryl group.

.Such' prior .art methods o-fproducing aromatic mercury halidesobviously involve great expense in the use'of costly organic solventsand large amounts of copper. Another disadvantage of the prior artmethods is the necessity of separating the intermediate product, namelythe double salt, from, the reaction mixture prior to proceeding with thedecompositionstep which produces the aryl mercury halide. I d Applicantshave simplified this involved, time consuming andcostly procedure bythe; use of a continuous and uninterrupted method of producirig saidaryl mercury halides. Another improvement of. the instant invention overthe prior art methods is the considerably increased yield obtainedhereby. The sum total of the above I more, the resultant products ofthis invention exhibit a particularly low solubility in water ren+dering them considerably more economical in halides.

2 use, said products maintaining their therapeutic activity over alonger period of time.

Accordingly, an object of the present invention is the development of anew process for the production of a high yield of aryl mercury Anotherobject of this invention is the development of a superior commercialprocess of manufacturing aryl mercury halides.

A further object of this invention is the development of a continuousand uninterrupted method of producing aryl or substituted aryl mercuryhalides.

A further object of this invention is the development of a simplifiedprocess of producingaryl mercury halides.

Further objects and advantages of the present invention will be apparentfrom the following description.

It has now been discovered that aromatic mercury halides may be preparedin a continuous mannerby diazotizing an aromatic amine at' a temperatureof about 0-5 C. to form the diazonium salt, introducing said diazoniumsalt into an acidic aqueous medium containing a mercury halide and anequivalent amount of cuprous halide, whereby a diazonium double saltwith mercury halide is formed which is immediately decomposed by saidcuprous halide to an arcmatic mercury halide according to the reaction:

wherein R represents an aromatic group and Y represents ahalide, andrecovering a substan tially pure aromatic mercury halide.

It has also been discovered, and constitutes an underlying principle ofthe present invention, that instead of powdered copper it is possible touse a cuprous halide for the decomposition of the diazonium double salt.It has been further found that this decomposition reaction is an' ionicone requiring only two electro-positive valences for the decompositionof the doublesalt, i. e., 1 gram-molecule of cuprous halide to 1grammolecule of the double salt. The resulting product, aryl mercuryhalide, shows a higher degree of purity and better quality than ifpowdered copper is used as the reducing agent.

It has also been discovered that the decomposition reaction is an ionicreaction and can be carried out in an aqueous medium or in the presenceof organic water miscible solvents or mixtures of water and organicwater miscible solvents. Furthermore, only two electro-positive valencesare necessary for the decomposition of the diazonium double salt.Consequently, one molecule of, double salt requires one molecule of acuprous halide which results in an 80% yield of the aromatic mercuryhalide. The decomposition reaction proceeds generally in accordance withthe following formula:

wherein X denotes any substituent from the group consisting of H, CH3,C2H5, OH, OCH3, OCzHs, Cl, Br, I, F, N02, COOH: R denotes an aryl group,and Y denotes one of the halogens Cl, Br, I.

Thus, an essential feature of the instant inven-- tion resides in theutilization of only one equivalent of cuprous halide, the total amountof 001)- per bein transformed into the water soluble cupric halideduring the decomposition reaction, as clearly illustrated by the abovechemical reaction. Thiseliminates the prior art step of separating theinsoluble cuprous chloride from the insoluble aryl mercury halide, thussimultaneously effecting a saving of organic solvent, since acetone isused in the above separation step.

Another important feature of the present process is the use of anaqueous medium for the decomposition reaction. This eliminates the useof expensive solvents heretofore utilized. Organic solvents misciblewith water, such as acetone, methanol, ethanol and the like, may beadded to the aqueous medium if a product of a higherdegree of purity isdesired. A mixture of water and organic water miscible solvent may beadvantageously used if a chemically pure product is desired. A smallquantity of certain impurities which normally would be precipitated withthe resultant product in an aqueous medium is eliminated from saidproduct in an aquepus organic medium due to the solubility of saidimpurities in a'mixture of water and organic solvent.

Another feature of the instant process is the use of an acidic mediumiorthe decomposition of the double diazonium salt. A neutral medium mayalso be utilized but it has been found that in .an acidic medium such ashydrochloric acid the reaction proceeds in a more favorable manner.

A further essential feature of the present process is the maintenance oftemperatures of about 5-10" C. during the decomposition reaction such asby the addition of ice to the reaction mixture.

The diazotizing reaction also occurs at temperatures of about 0-5' C. bysimultaneously cooling the reaction mixture during the formation of thediazonium compound '(RNzCl). The diazonium compound is prepared by theknown method of diazoti'zin an aromatic amine with sodium nitrite or thelike in the presence of hydrochloric acid or its equivalent.

A particular embodiment of this invention is the production of thediazonium double salt with mercury halide by adding'the diazonium saltto a suspension containing mercury halide and cuprous chloride, saidformed double salt being immediately reduced to the aromatic mercuryhalide by the cuprous chloride presentin the said suspension. Thereaction medium utilized for the formation of the double salt and itsalmost immediate reduction to the aromatic mercury halide is preferablyan acidified aqueous medium. The aqueous medium may also containwater-miscible organic solvents, if an unusually pure product isdesired. Thus, it is apparent that the formation of the double salt andits decomposition to the aromatic mercury halide is carried out in thesame medium, without the separation of any intermediate products.

The aryl-mercury bromide or iodide can be prepared by the same procedureas the chloride as represented by Equation No. 3. However, it is notnecessary to employ an exclusively bromide or iodide medium. Thedecomposition of the double diazonium mercury chloride salt may becarried out in a chloride medium such as hydrochloric acid, in thepresence of only one equivalent of a difierent soluble metallic halidesuch as the alkali metal bromide or iodide. The bromide and iodide ionsare more reactive than the chloride ions and consequently replace thechloride to form the corresponding aryl-mercury bromide or iodide, whichresults in a more insoluble halide of an aromatic mercury compound. Thereaction proceeds in accordance with the following formula, wherein Yrepresents Br or I, and Me represents Na or K:

Among the substantial advantages of the present invention is that asubstantially very pure product is obtained and that the entire courseof reaction takes place in a single phase without the interveningisolation of any of the intermediate products. Only the resultantcrystalline product, aryl mercury halide, is isolated, by suction afterthe entire cuprous halide employed for the decomposition reaction hasbeen dissolved and transformed into the soluble cupric halide.

This new process for the preparation of aryl mercury halides and similarcompounds according to the present invention represents a considerabletechnical advance as compared with the processes heretofore known andmay be used as a preferred commercial process for mass production. Theadvantages of the process according to the invention over the prior artprocesses are simplification of the entire course of the reaction, whichis carried out continuously in a single vessel without separation of theintermediate products, the expensive organic solvents for the extractionof the product are either not necessary at all or are used only in smallquantities if desired, the product exhibits a higher degree of purityand the yield is very good.

The following examples are additionally illustrative of the presentinvention andare not to be considered as limiting the scope thereof.

Example I litres of hydrochloric acid of a sp. gr. of 1.17 are cooled bymeans of 300 kgs. of ice broken into pieces the size of a fist, to which46.5 kgs. of aniline are added. Diazotization is carried out in thecustomary way by means of 3:5.0 kgs. of sodium nitrite at a temperaturenot exceeding 5 C. The above solution of benzene diazonium chloride isgradually introduced into a suspension which contains 100 litres ofhydrochloric acid of a sp. gr. of 1.17, 136 kgs. of mercuric chlorideand 99 kgs. of'cuprous chloride, CuzClz. This suspension is also beingcooled by the introduction of 200 kgsof ice broken into small pieces. Acrystalline paste of a double salt of benzene diazonium chloride withmercuric chloride is immediately produced, said paste being decomposedby the cuprous chloride present and reduced to phenyl mercury chloride.The-temperature during this reaction is maintained within the limits of5-'10 C. The decomposition of the double salt is terminated within onehour and -means of 35.0 kgs. of sodium nitrite.

the precipitated insoluble phenyl mercury chloride, CeHsHgCl, is removedby suction, washed with water and dried. The yield of the technicallypure product amounts to 120 kgs, which is 76.7% of the theoreticalyield. The melting point of the phenyl mercury chloride is 251 C. Theentire copper is in the form of soluble cupric chloride 'CuCh, whichremains dissolved in the mother liquor.

Example II 46.5 kgs. aniline and 65 kgs. of crystalline sodium bromideare introduced into 100 litres of hydrochloric acid-of a sp. gr. of 1.17and the solution is cooled by the additionof 300 kgs. of broken ice. Thesolution is then diazotized in the usual manner with 35.0 kgs. of sodiumnitrite at a temperature'not exceeding 5 C. The produced solution ofbenzene diazonium chloride is slowlyintroduced into a suspension, whichcontains 100 litres of hydrochloric acid of a sp. gr. of 1.17, 136 kgs.of mercuric chloride and 99 kgs. of cuprous chloride, CuzClz, and thesuspension is further cooled by gradually introducing 200 'kgs. ofbroken ice. the double salt of benzene diazonium chloride with mercuricchloride is immediately formed, said paste being decomposed by thecuprous chloride present and transformed into phenyl mer- 'cury bromide.The temperature during this reaction is maintained at 5 C. Thedecomposition of the double salt is'terminated within about 1 'hour andthe precipitated insoluble raw phenyl mercury bromide, CGHSHgBI', isremoved by suction, washed with water and dried. The yield of thetechnically pure product amounts of 141 kgs.

or 80% of the theoretical yield. The entire copper is dissolved in themother liquor in the form of soluble cupric chloride.

Erample III 53.5 kgs. of p-toluidine are introduced into 160 litres ofhydrobromic acid of a sp. gr. of 1.377 and the solution is cooled by theaddition of 300 kgs. of broken ice. The produced hydrobromide ofp-toluidine is diazotized in the usual way by The solution of p-methylbenzene diazonium bromide thus produced is gradually introduced into asolution of 180 kgs. of mercury bromide in 100 litres of hydrobromicacid of a sp. gr. of 1.377, cooled with 200 kgs. of ice, wherein 144kgs. of cuprous bromide are suspended. A double salt of p-methyl benzenediazonium bromide with mercury bromide is first formed which salt isimmediately decomposed by the cuprous bromide present and reduced top-tolyl mercury bromide,

The temperature during this decompo- Erample IV "sas es; ofp-nitroaniline are introduced into 110""litres of hydrochloric acid ofsp. gr. 1.17,' f :cooled with 200 kgs. of ice and diazotized in theusual manner at a temperature not exceeding 5 C. with 35.0 kg. of sodiumnitrite. The solution of (p-nitrobenzenc diazonium chloride formed is"gradually added to a solution containing 100 litres A crystalline pasteof 6 of hydrochloric acid of sp. gr. 1.17, 800 litres of ethanol, 136kgs. of mercury chloride, in which are suspended 99.0 kgs. of cuprouschloride,

The double salt, p-nitro-benzene-diazonium chloride with mercurychloride, produced atfirst is immediately decomposed by the cuprouschloride present and reduced with a simultaneous release of nitrogen toform p-nitro-phenyl mercury chloride NO2C6H4HgCL' The total amount ofcopper dissolves in the mother liquor in the form of cupric chloride,CllCIz. The temperature during this decomposition reaction is maintainedwithin the range of 0-5 C. .The precipitated technically pureproduct isremoved by suction, washed with water and dried. The yield amounts to77.0 kgs. or 43% of the theoretical yield. The melting point of theproduct is 263-26"? C.

It will be understood that each of the elements described above, or twoor more together, may also find a useful application in other types ofmethod of manufacturing halide differing from the types described above.

While we have illustrated and described the invention as embodied inmethods of manufacturing aromatic mercury halides, we do not intend tobe limited to the details shown, since 'various modifications andstructural changes may be made without departing in any way from thespirit of our invention.

Without further analysis, the foregoing will so fully reveal the gist ofour invention that others can by applying current knowledge readilyadapt it for various applications without omitting features that, fromthe standpoint of prior art, fairly constitute essential characteristicsof the generic or specific aspects of this invention and, therefore,such adaptations should and are intended to be comprehended within themeaning and range of equivalence of the following claims.

What we claim as new and desire to secure by Letters Patent is:

1. A commercial method of manufacturing an aromatic mercury halide whichcomprises diazotizing an aryl amine at a temperature of about 0-5 C. toform the diazonium salt, introducing said diazonium salt into an acidicaqueous medium containing a mercury halide and an equivalent amount ofcuprous halide, whereby a diazo nium double salt with mercury halide isformed which is immediately decomposed by said cuprous halide to an arylmercury halide according to the reaction: I

RN2Y.HgY2 Cll2Y2- RHgY-l- 2Cl1Yz +N2 wherein R represents an aryl groupand Y represents a halide, and recovering a substantially pure arylmercury halide.

2. A'commercial method of manufacturing an aromatic mercury halide whichcomprises diazotizing an aromatic amine at a temperature of about 05 C.to form the diazonium salt, introducing said diazonium salt into anacidic aqueous medium containing a mercury halide and an equivalentamount of cuprous halide, wherev by a diazonium double salt with mercuryhalide is formed Which is immediately decomposed by said cuprous halideto an aromatic mercury halide according to the reaction:

wherein R represents an aromatic group and Y aromatic mercury halidewhich comprises diazotizing a substituted aryl amine, said substituentbeing selected from the group consisting of CH3. C2H5, OH, OCH3, OCzHs,Cl, Br, I, F, N02, and COOH, at a temperature of about 5 C., to form thediazonium salt, introducing said diazonium salt into an acidic aqueousmedium containing a mercury halide and an equivalent amount of cuproushalide, whereby a diazonium double salt with mercury halide is formedwhich is immediately decomposed by said cuprous halide to a substitutedaryl mercury halide according to the reaction:

wherein R represents a substituted aryl group and Y represents a halide,and recovery a substantially pure substituted aryl mercury halide.

4. A commercial method of manufacturing an aromatic mercury halide whichcomprises diazotizing an aromatic amine at a temperature of about 0-5 C.to form the diazonium salt, introducing said diazonium salt into anacidic aqueous medium admixed with a Water-miscible organicsolvent'containing a mercury halide and an equivalent amount of cuporushalide, whereby a diazonium double salt with mercury halide is formedwhich is immediately decomposed by said cuprous halide to an aromaticmercury halide according to the reaction:

wherein R represents an aromatic group and Y represents a halide, andrecovering a substantially pure aromatic mercury halide.

5. A commercial method of manufacturing an aromatic mercury halide whichcomprises diazotizing an aryl amine at a temperature of about 0-7-5 C.to form the diazonium salt, reacting said salt with a mercury halide toform a diazonium double salt containing mercury halide, decomposing saiddouble salt at a temperature of about 5-10 C. in an acidic aqueousmedium by the addition of an equivalent weight of cuprous chloride toform an insoluble aryl mercury halide according to the reaction:

wherein R represents an aryl group and Y represents a halide andrecovering a substantially pure aryl mercury halide.

6. A commercial method of manufacturing an aromatic mercury halide whichcomprises diazotizing an aromatic amine at a temperature of about 0-5 G.to form the diazonium salt, reacting said salt with a mercury halide toform a diazonium double salt containing mercury halide, decomposing saiddouble salt at a temperature of about 5-l0 C. in an acidic aqueousmedium by the addition of an equivalent weight of cuprous chloride toform an insoluble aromatic mercury halide according to the reaction:

wherein represents an aromatic group and Y represents a halide, andrecovering a substantially pure aromatic mercury halide.

7. A commercial method of manufacturing an aromatic mercury halide whichcomprises diazotizing a substituted aryl amine at a temperature of about0-5 C. to form the diazonium salt, reacting said salt with a mercuryhalide to form a diazonium double salt containing mercury halide,decomposing said double salt at a temperature of about 540 C. in anacidic aqueous medium by the addition of an equivalent weight of cuprouschloride to form an insoluble substituted aryl mercury halide accordingto the reaction:

wherein R represents a substituted aryl group and Y represents a halide,and recovering a substantially pure substituted aryl mercury halide.

8. A commercial method of manufacturing an aromatic mercury halide whichcomprises diazotizing an aryl amine at a temperature of about 0-5 C. toform the diazonium salt, reacting said salt with a mercury halide toform a diazonium double salt containing mercury halide, decomposing saiddouble salt at a temperature of about 5-10 C. in an acidic aqueousmedium containing a water-miscible organic solvent by the addition of anequivalent weight of cuprous chloride to form an insoluble aryl mercuryhalide according to the reaction:

wherein R represents an aryl group and Y represents a halide, andrecovering a substantially pure aryl mercury halide.

9. A commercial method of manufacturing an aromatic mercury halide whichcomprises diazotizing an aryl amine at a temperature of about 05 C. toform the diazonium salt, reacting said salt with a mercury halide toform a diazonium double salt containing mercury halide. decomposing saiddouble salt in the presence of one equivalent of a soluble halide salt,said halide being difierent from the halide in the double salt, at atemperature of about 5-l0 C. in-an acidic aqueous medium by the additionof an equivalent weight of cuprous chlorideto form an insoluble arylmercury halide and recovering a substantially pure aryl mercury halide.

10. A commercial methodof manufacturing an aromatic mercury halide whichcomprises diazotizing an aryl amine at a temperature of about 05 C. toform the diazonium salt, reacting said salt with a mercury chloride toform a diazonium double salt containing mercury chloride, decomposingsaid double salt, in the presence of an equivalent amount of a solublehalide salt selected from the class consisting of NaBr, NaI, KBr and KI,at a temperature of about 5-10 C. in an acidic aqueous medium by theaddition of an equivalent weight of cuprous chloride to form aninsoluble aryl mercury halide and recovering a substantially pure arylmercury halide.

11. A commercial method of manufacturing an aromatic mercury halidewhich comprises diazotizing an aromatic amine at a temperature of about0-5 C. to form the diazonium salt, reacting said salt with a mercuryhalide to form a diazonium double salt containing mercury halide,decomposing said double salt in the presence of an equivalent amount ofa soluble halide salt selected from the class consisting of NaBr, NaI,KBr and KI, at a temperature of about 5-10 C. in an acidic aqueousmedium by the addition of an equivalent weight of cuprous chloride toform an insoluble aromatic mercury halide, and recovering asubstantially pure aromatic mercury halide.

12. A commercial method of manufacturing an aromatic mercury halidewhich comprises diazotizing a substituted aryl amine at a temperature ofabout 0-5 C. to form the diazonium salt, reacting said salt with amercury halide to form a diazonium double salt containing mercuryhalide, decomposing said double salt in the presence of an equivalentamount of a soluble halide salt selected from the class consisting ofNaBr, NaI, KBr and KI, at a temperature of about 5-l0'C. in an acidicaqueous medium by the addition of an equivalent weight of cuprouschloride to form an insoluble substituted aryl mercury halide, andrecovering a substantially pure substituted aryl mercury halide.

13. A commercial method of manufacturing an aromatic mercury halidewhich comprises diazotizing an aryl amine at a temperature of about -5"C. to form the diazonium salt, reacting said salt with a mercury halideto form a diazonium double salt containing mercury halide, decomposingsaid double salt to the presence of an equivalent amount of a solublhalide salt selected from the class consisting of NaBr, NaI, KBr andKLat a temperature of about -10 C. in an acidic aqueous mediumcontaining a watermiscible organic solvent by the addition of anequivalent weight of cuprous chloride to form an insoluble aryl mercuryhalide, and recovering a substantially pure aryl mercury halide.

14. A commercial method of manufacturing an aromatic mercury halidewhich comprises diazotizing an aryl amine at a temperature of about 0-5C. to form the diazonium salt, reacting said salt with a mercury halideto form a diazonium double salt containing mercury halide, decomposingsaid double salt at a temperature of about 5-10 C. in an acidic aqueousmedium by the addition of an equivalent weight of cuprous chloride toform an insoluble aryl mercury halide according to the reaction:

wherein R represents an aryl group and Y represents a halide, separatingthe insoluble aryl mercury halide from the aqueous medium and recoveringa substantially pure aryl mercury halide.

15. A commercial method of manufacturing an aromatic mercury halidewhich comprises diazotizing an aryl amine at a temperature of about 0-5C. to form the diazonium salt, introducing said diazonium salt into anacidic aqueous medium admixed with a water-miscible organic solventcontaining a mercury halide and an equivalent amount of cuprous halide,whereby a diazonium double salt with mercury halide is formed which isimmediately decomposed by said cuprous halide to an aryl mercury halideaccording to the reaction:

wherein R represents an aryl group and Y represents a halide, separatingthe insoluble aryl mercury halide from the aqueous medium and recoveringa substantially pure aryl mercury halide.

16. A commercial method of manufacturing an aromatic mercury halidewhich comprises diazotizing an aryl amine at a temperature of about 0-5C. to form the diazonium salt, introducing said diazonium salt into anacidic aqueous medium containing mercury chloride, an equivalent amountof cuprous chloride and an equivalent amount of a soluble halide saltselected from the class consisting of NaBr, NaI, KBr and KI, whereby adiazonium salt with mercury chloride is formed which is immediatelydecomposed by said cuprous halide to an aryl mercury halide, said halidebeing selected from the group consisting of Br and I, and recovering asubstantially pure aryl mercury halide.

OTTO DANEK. JAROSLAV NOSEK.

REFERENCES CITED The following references are of record in the file ofthis patent:

Nesmejanow et al., Ber., vol. 67, pages -134 (1934).

Nesmejanow, Ber., vol. 62, pages 1010-1018 (1929).

Nesmejanow et al., Ber., vol. 68, pages 1877- 1883 (1935) Nesmejanow etal., Chem. Centralblatt, 1935 II, page 389.

1. A COMMMERCIAL METHOD OF MANUFACTURING AN AROMATIC MERCURY HALIDE WHICH COMPRISING DIAZOTIZING AN ARYL AMINE AT A TEMPERATURE OF ABOUT 0-5* C. TO FORM THE DIAZONIUM SALT, INTRODUCING SAID DIAZONIUM SALT INTO AN ACIDIC AQUEOUS MEDIUM CONTAINING A MERCURY HALIDE AND AN EQUIVALENT AMOUNT OF A CUPROUS HALIDE, WHEREBY A DIAZONIUM DOUBLE SALT WITH MERCURY HALIDE IS FORMED WHICH IS IMMEDIATELY DECOMPOSED BY SAID CUPROUS HALIDE TO AN ARYL MERCURY HALIDE ACCORDING TO THE REACTION: 